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KMID : 0043320210440020182
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Archives of Pharmacal Research
2021 Volume.44 No. 2 p.182 ~ p.193
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Hyperthermal paclitaxel-bound albumin nanoparticles co-loaded with indocyanine green and hyaluronidase for treating pancreatic cancers
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Kim Sung-Soo
Kim Hwang-Kyung
Kim Han-Ju
Lee Woo-Tak
Lee Eun-Seong
Oh Kyung-Taek
Choi Han-Gon
Youn Yu-Seok
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Abstract
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Albumin nanoparticles have become an attractive cancer nanomedicine platform due to their pharmaceutical advantages. Recently, photothermal therapy has been extensively applied to cancer treatment due to heat-induced tumor ablation. Herein, we fabricated albumin nanoparticles (HSA-NPs) loaded with paclitaxel (PTX), indocyanine green (ICG; a hyperthermal agent) and hyaluronidase (HAase) that breaks down hyaluronan, a major component of the extracellular matrix (ECM) in tumors. Synthesis was based on a slightly modified nanoparticle albumin-bound (Nab™) technique. The prepared nanoparticles (PTX/ICG/HAase-HSA-NPs) had a spherical shape with an average size of ~?110 nm and a zeta potential of ~ -30.4 mV. They displayed good colloidal stability and typical patterns of ICG, HSA and HAase in UV?VIS?NIR and circular dichroism spectroscopic analysis. PTX/ICG/HAase-HSA-NPs were found to have excellent hyperthermal effects in response to near-infrared laser irradiation (808 nm) (up to >?50 °C over 4 min). The hyperthermia conducted by PTX/ICG/HAase-HSA-NPs resulted in significant cytotoxicity to pancreatic AsPC-1 cells at both severe (>?50 °C) and mild (41?42 °C) hyperthermal states in conjunction with the inherent cytotoxic activity of paclitaxel. Furthermore, the confocal images of AsPC-1 cell spheroids proved PTX/ICG/HAase-HSA-NPs were able to permeate deeply into the three-dimensional tumor tissue mimicry structure. Most of all, PTX/ICG/HAase-HSA-NPs maintained all these physicochemical and anti-cancer properties irrespective of the amount of embedded HAase (1?5 mg). Our results demonstrated that PTX/ICG/HAase-HSA-NPs are a promising hyperthermal/chemotherapeutic anticancer agent.
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KEYWORD
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Indocyanine green, Hyaluronidase, Hyperthermal therapy, Albumin nanoparticles, Tumor targeting
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